9,10-Dihydro-pyrrolo[2,1-b][1,3]benzothiazepines are described in international patent application WO 00/06579, which is incorporated herein in its entirety for reference purposes, as compounds endowed with antipsychotic activity, with particular reference to the treatment of psychoses, such as schizophrenia, paranoid states, manic-depressive states, emotional disorders, antisocial behaviour, personality regression, and hallucinations.
For the compounds described in the patent application cited above, processes are provided for their preparation which involve the cyclisation reaction of a derivative containing a phenyl group and a pyrrol group, leading to the formation of a [1,3]-thiazepine ring. Preferably, the cyclisation should lead to a pyrrolo-benzothiazepinone derivative, which is then transformed into the desired 9-amino-substituted pyrrolo[2,1-b][1,3]benzothiazepine by acting on the ketone group.
The transformation of the ketone group to an amine group, optionally substituted, entails a certain number of steps. As illustrated in diagram 2B/2 of the patent application cited above, the ketone group is first reduced to a hydroxy group, which in turn is substituted with a suitable leaving group, for example a bromine atom, and finally the amine group desired is inserted. The transformation of the ketone group to a final amine group generates a chiral centre, and the resulting racemic mixture which derives from it is finally separated into the individual enantiomorphs with traditional methods. The substitution of the hydroxy group with the leaving group (bromine in the example given) entails a lowering of the yield, which the next step is unable to recover on a scale preparation plan.